Iberverin exhibits antineoplastic activities against human hepatocellular carcinoma via DNA damage-mediated cell cycle arrest and mitochondrial-related apoptosis

Hepatocellular carcinoma (HCC) is one of the malignant tumors with high incidence and mortality rates in the world. Isothiocyanates (ITCs), bioactive substances present primarily in the plant order Brassicales, have been proved to be promising candidates for novel anti-HCC drugs with chemopreventive and anticancer activities. Iberverin, a predominant ITC isolated from the seeds of oxheart cabbage, has been discovered with anticancer property in lung cancer cells. However, the roles of iberverin in HCC remain elusive. In the present study, the effect and potential mechanisms of iberverin against human HCC were dissected. We demonstrated that low concentrations of iberverin inhibited cell proliferation, suppressed migration and induced mitochondrial-related apoptosis in vitro, and hampered tumorigenicity in vivo, with no obvious toxicity. Furthermore, we found that iberverin treatment induced DNA damage and G2/M phase arrest. Iberverin treatment also caused increased intracellular reactive oxygen species formation and glutathione depletion. Taken together, these results suggest that iberverin promotes mitochondrial-mediated apoptosis and induces DNA damage and G2/M cell cycle arrest in HCC by enhancing oxidative stress. Our findings provide better understanding of the anti-HCC mechanisms of ITCs and the potential for the natural product iberverin as a promising new anti-HCC biotherapeutic

Can integration reduce inequity in healthcare utilization?: evidence and hurdles in China

Background: Integration of medical insurance schemes has been prioritized as one of the key strategies to address inequity in China's health system. The first pilot attempt to integrate started in 2003 and later expanded nationwide. This study aims to assess its intended impact on inequity in inpatient service utilization and identify the main determinants contributing to ieffectiveness. Methods: A total of 49,365 respondents in the pilot integrated area and 77,165 respondents in the non-integration area were extracted from the Fifth National Health Services Survey. A comparative analysis was conducted between two types of areas. We calculate a concentration index (CI) and horizontal inequity index (HI) in inpatient service utilization and decompose the two indices. Results: Insurance integration played a positive role in reducing inequality in inpatient service utilization to some extent. A 13.23% lower in HI, a decrease in unmet inpatient care and financial barriers to inpatient care in the pilot integrated area compared with the non-integration area; decomposition analysis showed that the Urban-Rural Residents Basic Medical Insurance, a type of integrated insurance, contributed 37.49% to reducing inequality in inpatient service utilization. However, it still could not offset the strong negative effect of income and other insurance schemes that have increased inequality. Conclusions: The earlier pilot attempt for integrating medical insurance was not enough to counteract the influence of factors which increased the inequality in inpatient service utilization. Further efforts to address the inequality should focus on widening access to financing, upgrading the risk pool, reducing gaps within and between insurance schemes, and providing broader chronic disease benefit packages. Social policies that target the needs of the poor with coordinated efforts from various levels and agencies of the government are urgently needed

Macleaya cordata isoquinoline alkaloids attenuate Escherichia coli lipopolysaccharide-induced intestinal epithelium injury in broiler chickens by co-regulating the TLR4/MyD88/NF-κB and Nrf2 signaling pathways

This study sought to explore the effects and potential mechanisms of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata to alleviate lipopolysaccharide (LPS)-induced intestinal epithelium injury in broilers. A total of 486 1-day-old broilers were assigned at random to a control (CON) group, LPS group, and LPS+IA group in a 21-d study. The CON and LPS groups received a basal diet, while the LPS+IA group received a basal diet supplemented with 0.6 mg/kg IA. At 17, 19, and 21 days of age, the LPS and LPS+BP groups were injected intraperitoneally with LPS, and the CON group was intraperitoneally injected equivalent amount of saline solution. The results manifested that LPS injection caused intestinal inflammation and lipid peroxidation, disrupted intestinal barrier and function, and increased the abundance of harmful microorganisms. However, dietary IA supplementation alleviated LPS-induced adverse changes in intestinal morphology, apoptosis, mucosal barrier integrity, cecum microorganisms, and homeostasis disorder by decreasing inflammatory cytokines and enhancing antioxidant-related genes expressions; inhibited LPS-induced increases in TLR4 and NF-κB expressions and decreases in Nrf2 and GPX1 genes expressions. Our findings indicated that Macleaya cordata IA addition attenuated LPS-induced intestinal epithelium injury and disorder of intestinal homeostasis by enhancing the anti-inflammatory and antioxidant capacity of broiler chickens possibly via co-regulating TLR4/MyD88/NF-κB and Nrf2 signaling pathways

Video delivery networks : challenges, solutions and future directions

Internet video ecosystems are faced with the increasing requirements in versatile applications, ubiquitous consumption and freedom of creation and sharing, in which the user experience for high-quality services has become more and more important. Internet is also under tremendous pressure due to the exponential growth in video consumption. Video providers have been using content delivery networks (CDNs) to deliver high-quality video services. However, the new features in video generation and consumption require CDN to address the scalability, quality of service and flexibility challenges. As a result, we need to rethink future CDN for sustainable video delivery. To this end, we give an overview for the Internet video ecosystem evolution. We survey the existing video delivery solutions from the perspective of economic relationships, algorithms, mechanisms and architectures. At the end of the article, we propose a data-driven information plane for video delivery network as the future direction and discuss two case studies to demonstrate its necessity

May 22, 2006 22:28 WSPC/Trim Size: 11in x 8.5in for Proceedings csb2006 Protein Fold Recognition Using the Gradient Boost Algorithm

Protein structure prediction is one of the most important and difficult problems in computational molecular biology. Protein threading represents one of the most promising techniques for this problem. One of the critical steps in protein threading, called fold recognition, is to choose the best-fit template for the query protein with the structure to be predicted. The standard method for template selection is to rank candidates according to the z-score of the sequence-template alignment. However, the z-score calculation is time-consuming, which greatly hinders structure prediction at a genome scale. In this paper, we present a machine learning approach that treats the fold recognition problem as a regression task and uses a least-squares boosting algorithm (LS Boost) to solve it efficiently. We test our method on Lindahl’s benchmark and compare it with other methods. According to our experimental results we can draw the conclusions that: (1) Machine learning techniques offer an effective way to solve the fold recognition problem. (2) Formulating protein fold recognition as a regression rather than a classification problem leads to a more effective outcome. (3) Importantly, the LS Boost algorithm does not require the calculation of the z-score as an input, and therefore can obtain significant computational savings over standard approaches. (4) The LS Boost algorithm obtains superior accuracy, with less computation for both training and testing, than alternative machine learning approaches such as SVMs and neural networks, which also need not calculate the z-score. Finally, by using the LS Boost algorithm, one can identify important features in the fold recognition protocol, something that cannot be done using a straightforward SVM approach. 1

Impact of Urban Undersea Tunnel Longitudinal Slope on the Visual Characteristics of Drivers

This study aims to investigate the impact of the urban undersea tunnel longitudinal slope on the visual characteristics of drivers. 20 drivers were enrolled to conduct the real vehicle test of the urban undersea tunnel. First, the data of average fixation time and visual lobe were collected by an eye tracker. The differential significance was tested using the one-way repeated measures analysis of variance (ANOVA). Then, the difference between the up-and-down slope (direction) factor and the longitudinal slope (percent) factor on the two indexes were analyzed using the two-way repeated measures ANOVA. Second, by constructing a Lorentz model, the impact of the longitudinal slope on the average fixation time and the visual lobe were analyzed. Besides, a three-dimensional model of the longitudinal slope, average fixation time, and visual lobe was quantified. The results showed that the average fixation time and visual lobe under different longitudinal slopes markedly differed when driving on the uphill and downhill sections. The average fixation time and visual lobe under two factors were markedly different. Moreover, with an increase in the longitudinal slope, the average fixation time exhibited a trend of increasing first then decreasing; the visual lobe exhibited a trend of decreasing first and then increasing. The average fixation time reached the minimum and maximum value when the slope was 2.15% and 4.0%, whereas the visual lobe reached the maximum and minimum value when the slope was 2.88% and 4.0%. Overall, the longitudinal slope exerted a great impact on the visual load of the driver

BCAT1 controls embryonic neural stem cells proliferation and differentiation in the upper layer neurons

Abstract The regulation of neural stem cell (NSC) proliferation and differentiation during brain development is a precisely controlled process, with the production of different neuronal subtypes governed by strict timelines. Glutamate is predominantly used as a neurotransmitter by the subtypes of neurons in the various layers of the cerebral cortex. The expression pattern of BCAT1, a gene involved in glutamate metabolism, in the different layers of neurons has yet to be fully understood. Using single-cell data, we have identified seven different states of NSCs and found that state 4 is closely associated with the development of projection neurons. By inferring the developmental trajectory of different neuronal subtypes from NSC subsets of this state, we discovered that BCAT1 is involved in the regulation of NSC proliferation and differentiation and is specifically highly expressed in layer II/III and IV neurons. Suppression of BCAT1 through shRNA resulted in a reduction in NSC proliferation and an abnormal development of layer II/III and IV neurons. These findings provide new insights into the role of BCAT1 in the regulation of NSC behavior and neuronal development